Cerebral vascular calcium signaling in diabetic Alzheimer's disease-related dementias

糖尿病阿尔茨海默病相关痴呆的脑血管钙信号传导

基本信息

  • 批准号:
    10117843
  • 负责人:
  • 金额:
    $ 32.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-03-15 至 2024-08-28
  • 项目状态:
    已结题

项目摘要

Alzheimer's disease (AD) and AD-related dementias (ADRD) are the common incurable neurodegenerative even conditions characterized by progressive cognitive deterioration, memory decline and death. The major forms of ADRD include vascular contributions to cognitive impairment and dementia (VCID). In agreement, vascular dementia is the second most common form of dementia and the most frequent comorbidity with AD. Diabetes may production is a leading factor in the development of VCID; the ole of diabetes primarily occur due to the abnormal glucose metabolism and i ncreased reactive oxygen species (ROS) in cerebral vascular smooth muscle cells (CASMCs) r . In support, antioxidant therapies have shown promising results in protecting against diabetes-induced VCID and other dementias. the molecular mechanisms that link diabetes to the development of VCID remain to be elucidated, and current treatments for these diseases are neither always effective nor specific. The Based on our preliminary findings with previous work, in this project, we propose a novel central hypothesis that diabetes increases Rieske iron-sulfur protein (RISP)-mediated mitochondrial ROS, dissociates FK506 binding protein 12.6 (FKBP12.6) from type-2 ryanodine receptor (RyR2) to remove its inhibitory effect on RyR2 channel and induce Ca2+ release, which causes cerebral vasoconstriction and cerebral blood flow reduction, thereby leading to progressive memory loss, cognitive decline and VCID. To test this exciting hypothesis, we will conduct a series of mechanistic studies primarily by employing smooth muscle-specific RISP, RyR2, and FKBP12.6 knockout (KO) and/or overexpression (OE) mice with other complementary advanced experimental approaches to address the following specific questions (Specific Aims): Aim 1: Are the increased RISP-mediated mitochondrial ROS in CASMCs essential for VCID induced by diabetes? Aim 2: Is RyR2/FKBP12.6 complex dissociation a key consequence for the increased RISP-mediated mitochondrial ROS to mediate VCID induced by diabetes? The objectives of the present proposal are not only to enhance our understanding of the molecular mechanisms for VCID, ADRD devastating diseases. and AD, but also help to identify novel therapeutic targets for these common
阿尔茨海默病(AD)和AD相关性痴呆(ADRD)是常见的无法治愈的疾病

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mitochondrial Dynamics in Pulmonary Hypertension.
  • DOI:
    10.3390/biomedicines12010053
  • 发表时间:
    2023-12-25
  • 期刊:
  • 影响因子:
    4.7
  • 作者:
  • 通讯作者:
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YONG-XIAO WANG其他文献

YONG-XIAO WANG的其他文献

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{{ truncateString('YONG-XIAO WANG', 18)}}的其他基金

Novel signaling in chronic hypoxic responses in pulmonary arteries
肺动脉慢性缺氧反应的新信号传导
  • 批准号:
    9186562
  • 财政年份:
    2014
  • 资助金额:
    $ 32.6万
  • 项目类别:
Novel signaling in chronic hypoxic responses in pulmonary arteries
肺动脉慢性缺氧反应的新信号传导
  • 批准号:
    8979717
  • 财政年份:
    2014
  • 资助金额:
    $ 32.6万
  • 项目类别:
Novel signaling in chronic hypoxic responses in pulmonary arteries
肺动脉慢性缺氧反应的新信号传导
  • 批准号:
    8825232
  • 财政年份:
    2014
  • 资助金额:
    $ 32.6万
  • 项目类别:
Signaling Mechanisms for Hypoxic Pulmonary Vasoconstriction
缺氧肺血管收缩的信号机制
  • 批准号:
    8389620
  • 财政年份:
    2012
  • 资助金额:
    $ 32.6万
  • 项目类别:
Signaling Mechanisms for Hypoxic Pulmonary Vasoconstriction
缺氧肺血管收缩的信号机制
  • 批准号:
    8598510
  • 财政年份:
    2012
  • 资助金额:
    $ 32.6万
  • 项目类别:
Signaling Mechanisms for Hypoxic Pulmonary Vasoconstriction
缺氧肺血管收缩的信号机制
  • 批准号:
    8237425
  • 财政年份:
    2012
  • 资助金额:
    $ 32.6万
  • 项目类别:
Signaling Mechanisms for Hypoxic Pulmonary Vasoconstriction
缺氧肺血管收缩的信号机制
  • 批准号:
    8882527
  • 财政年份:
    2012
  • 资助金额:
    $ 32.6万
  • 项目类别:
Mechanisms for hypoxic Ca2+ release in pulmonary artery myocytes
肺动脉肌细胞缺氧释放Ca2+的机制
  • 批准号:
    7839422
  • 财政年份:
    2009
  • 资助金额:
    $ 32.6万
  • 项目类别:
Heterogeneity of hypoxic Ca2+ release in pulmonary and *
肺和 * 中缺氧 Ca2 释放的异质性
  • 批准号:
    7104320
  • 财政年份:
    2003
  • 资助金额:
    $ 32.6万
  • 项目类别:
Heterogeneity of hypoxic Ca2+ release in pulmonary and *
肺和 * 中缺氧 Ca2 释放的异质性
  • 批准号:
    6927284
  • 财政年份:
    2003
  • 资助金额:
    $ 32.6万
  • 项目类别:

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